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1.
Article in English | WPRIM | ID: wpr-929232

ABSTRACT

Natural products (NPs), especially those from traditional herbal medicines, can evidently modulate human gene expression at multiple levels, leading to a wide diversity of bioactivities. Although numerous bio-functions of NPs for human body have been found, there is little understanding about how NPs achieve it, as less attention was drawn to the definite mechnism by which NPs regulate gene expression. Furthermore, based on the rapidly advancing knowledge of mechanisms for gene regulation in recent years, newly-understood mechanisms, such as post-transcriptional regulation, are found to be involved in NP-elicited bio-effects, providing a new perspective on understanding the role of NPs in gene expression. Therefore, in the current review, we summarize the function of NPs in gene expression from the perspectives of transcriptional, post-transcriptional, and post-translational regulation, which will reinforce the understanding of NP-induced effects in gene expression and facilitate the exploration of more NPs with potential therapeutic effects.


Subject(s)
Biological Products/pharmacology , Gene Expression , Gene Expression Regulation , Humans
2.
Chinese Journal of Biotechnology ; (12): 1859-1873, 2022.
Article in Chinese | WPRIM | ID: wpr-927823

ABSTRACT

Leptin receptor overlapping transcript (LepROT) plays multiple roles in the regulation of immune systems. However, very little information is available about the anti-infectious mechanisms of amphibians LepROT. In this study, the cDNA sequence of the Rana dybowskii LepROT gene was determined by using RT-PCR and bioinformatics analysis. Then, the Aeromonas hydrophila (Ah) and lipopolysaccharides (LPS) infected models of R. dybowskii was constructed to obtain histopathological characteristics. Constitutive expression of LepROT mRNA and NF-κB signaling pathway were detected by real-time quantitative PCR. The full-length cDNA of LepROT gene was 396 bp and encoded 131 amino acids. Amino acid sequence analysis revealed LepROT shares 93.74% and 86.39% identity with homologues from other amphibians and mammals respectively, and the LepROT gene was quite conserved among different species. After infection, the relative expression levels of LepROT, NF-κB, IKKα and IKKβ mRNA were all significantly upregulated (P < 0.01), but showed a diverse temporal pattern of up-regulation in different tissues. Therefore, it was proposed that the LepROT gene of R. dybowskii might activate the NF-κB signaling pathway to exert anti-infectious effects, thus providing evidence for further extending the biological function of LepROT.


Subject(s)
Animals , Cloning, Molecular , DNA, Complementary , Gene Expression Profiling , Gene Expression Regulation , Mammals/metabolism , NF-kappa B/genetics , Phylogeny , RNA, Messenger/genetics , Ranidae/genetics
3.
Article in English | WPRIM | ID: wpr-929029

ABSTRACT

β-thalassemia (β-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present. The birth of children with moderate and severe β-thal brings economic pressure to families, social medical and health services. Long noncoding RNA (lncRNA) is a type of noncoding protein transcripts with a length greater than 200 nucleotides, which is involved in a variety of biological processes, such as cell proliferation, differentiation and chromosome variation and plays an important role in the epigenetic and post-transcriptional regulation of genes. It has potential value in the diagnosis, prevention and treatment of β-thal. LncRNA possesses the characteristics such as tissue specificity, cell specificity, developmental stage specificity, space-time specificity and disease specificity, and its complex interaction network has become a challenge to translate research results into clinical practice. Taking lncRNA as an entry point, in-depth understanding of the function of lncRNA in β-thal and explanation of its related regulatory mechanisms will provide theoretical basis for targeting treatment of β-thal, which can improve the diagnosis and treatment of β-thal.


Subject(s)
Cell Differentiation , Child , Gene Expression Regulation , Humans , RNA, Long Noncoding/genetics , beta-Thalassemia/therapy
4.
Electron. j. biotechnol ; 51: 50-57, May. 2021. ilus, graf
Article in English | LILACS | ID: biblio-1343384

ABSTRACT

BACKGROUND: Molecular brain therapies require the development of molecular switches to control gene expression in a limited and regulated manner in time and space. Light-switchable gene systems allow precise control of gene expression with an enhanced spatio-temporal resolution compared to chemical inducers. In this work, we adapted the existing light-switchable Light-On system into a lentiviral platform, which consists of two modules: (i) one for the expression of the blue light-switchable transactivator GAVPO and (ii) a second module containing an inducible-UAS promoter (UAS) modulated by a light-activated GAVPO. RESULTS: In the HEK293-T cell line transfected with this lentiviral plasmids system, the expression of the reporter mCherry increased between 4 to 5 fold after light induction. A time expression analysis after light induction during 24 h revealed that mRNA levels continuously increased up to 9 h, while protein levels increased throughout the experiment. Finally, transduction of cultured rat hippocampal neurons with this dual Light-On lentiviral system showed that CDNF, a potential therapeutic trophic factor, was induced only in cells exposed to blue light. CONCLUSIONS: In conclusion, the optimized lentiviral platform of the Light-On system provides an efficient way to control gene expression in neurons, suggesting that this platform could potentially be used in biomedical and neuroscience research, and eventually in brain therapies for neurodegenerative diseases.


Subject(s)
Gene Expression Regulation , Optogenetics/methods , Light , Neurons/metabolism , Immunoblotting , Gene Expression , Fluorescent Antibody Technique , Lentivirus
5.
Rev. Hosp. Ital. B. Aires (2004) ; 41(1): 37-42, mar. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1178964

ABSTRACT

El término CRISPR, por su acrónimo en inglés refiere a Clustered Regularly Interspaced Short Palindromic Repeats, es decir, repeticiones palindrómicas cortas, agrupadas y regularmente esparcidas, por sus características en el genoma, pertenece naturalmente al sistema de defensa de bacterias y arqueas. Este ha sido adaptado biotecnológicamente para la edición del ADN de células eucariotas, incluso de células humanas. El sistema CRISPR-Cas para editar genes consta, en forma generalizada, de dos componentes: una proteína nucleasa (Cas) y un ARN guía (sgRNA). La simplicidad del complejo lo hace una herramienta molecular reprogramable capaz de ser dirigida y de editar cualquier sitio en un genoma conocido. Su principal foco son las terapias para enfermedades hereditarias monogénicas y para el cáncer. Sin embargo, además de editor de genes, la tecnología CRISPR se utiliza para edición epigenética, regulación de la expresión génica y método de diagnóstico molecular. Este artículo tiene por objetivo presentar una revisión de las aplicaciones de la herramienta molecular CRISPR-Cas, particularmente en el campo biomédico, posibles tratamientos y diagnósticos, y los avances en investigación clínica, utilizando terapia génica con CRISPR/Cas más relevantes hasta la fecha. (AU)


CRISPR are Clustered Regularly Interspaced Short Palindromic Repeats, which naturally belong to the defense system of bacteria and archaea. It has been biotechnologically adapted for editing the DNA of eukaryotic cells, including human cells. The CRISPR-Cas system for editing genes generally consists of two components, a nuclease protein (Cas) and a guide RNA (sgRNA). The simplicity of the complex makes it a reprogrammable molecular tool capable of being targeted and editing any site in a known genome. Its main focus is therapies for monogenic inherited diseases and cancer. However, in addition to gene editor, CRISPR technology is used for epigenetic editing, regulation of gene expression, and molecular diagnostic methods. This article aims to present a review of the applications of the CRISPR-Cas molecular tool, particularly in the biomedical field, possible treatments and diagnoses, and the advances in clinical research, using the most relevant CRISPR-Cas gene therapy to date. (AU)


Subject(s)
Humans , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , CRISPR-Cas Systems/genetics , Biotechnology , Genetic Therapy/methods , Gene Expression , Genome, Human/genetics , Gene Expression Regulation , Epigenomics/trends , CRISPR-Associated Proteins/genetics , CRISPR-Associated Proteins/therapeutic use , Genetic Diseases, Inborn/therapy , Neoplasms/therapy
6.
Journal of Biomedical Engineering ; (6): 1010-1017, 2021.
Article in Chinese | WPRIM | ID: wpr-921840

ABSTRACT

The emergence of single-cell sequencing technology enables people to observe cells with unprecedented precision. However, it is difficult to capture the information on all cells and genes in one single-cell RNA sequencing (scRNA-seq) experiment. Single-cell data of a single modality cannot explain cell state and system changes in detail. The integrative analysis of single-cell data aims to address these two types of problems. Integrating multiple scRNA-seq data can collect complete cell types and provide a powerful boost for the construction of cell atlases. Integrating single-cell multimodal data can be used to study the causal relationship and gene regulation mechanism across modalities. The development and application of data integration methods helps fully explore the richness and relevance of single-cell data and discover meaningful biological changes. Based on this, this article reviews the basic principles, methods and applications of multiple scRNA-seq data integration and single-cell multimodal data integration. Moreover, the advantages and disadvantages of existing methods are discussed. Finally, the future development is prospected.


Subject(s)
Base Sequence , Gene Expression Profiling , Gene Expression Regulation , Humans , Sequence Analysis, RNA , Single-Cell Analysis
7.
Chinese Journal of Biotechnology ; (12): 3310-3322, 2021.
Article in Chinese | WPRIM | ID: wpr-921427

ABSTRACT

The effect of altering the promoter region of ubiquitous chromatin-opening element (UCOE) and matrix attachment region (MAR) on stable and efficient expression of genes was investigated. Four different promoters were tested, namely, oct4 containing an enhancer region, sox2 having a CpG island, nanog having no regulatory elements, and CMV containing a CpG island and an enhancer region. Eight reporter plasmids were constructed: pOCT4-UCOE, pOCT4-MAR, pSOX2-UCOE, pSOX2-MAR, pNANOG-UCOE, pNANOG-MAR, pCMV-UCOE, and pCMV-MAR. Stable and efficient expression was observed when UCOE combined with the oct4 promoter, whereas the sox2 was the best promoter suited for MAR. Comparison of the stable clones of oct4-UCOE and sox2-MAR showed that UCOE-regulated expression is more stable and efficient than MAR-regulated expression. When CpG island-containing promoter is linked with UCOE, stable and efficient expression could be observed. These data suggest that an enhancer region in the promoter leads to high, yet unstable expression when combined with UCOE, whereas CpG islands stabilize expression. In conclusion, UCOE and MAR interact with regulatory elements on the promoter by altering the chromatin open state and chromatin loop to regulate gene expression.


Subject(s)
Chromatin/genetics , CpG Islands/genetics , Gene Expression , Gene Expression Regulation , Promoter Regions, Genetic/genetics
8.
Article in English | WPRIM | ID: wpr-921331

ABSTRACT

Objective@#The expression patterns of ribosomal large subunit protein 23a (RPL23a) in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23a expression and spermatogonia apoptosis upon exposure to X-ray.@*Methods@#Male mice and GC-1 cells were irradiated with X-ray, terminal dUTP nick end-labelling (TUNEL) was performed to detect apoptotic spermatogonia @*Results@#Ionizing radiation (IR) increased spermatogonia apoptosis, the expression of RPL11, MDM2 and p53, and decreased RPL23a expression in mice spermatogonia @*Conclusion@#These results suggested that IR reduced RPL23a expression, leading to weakened the RPL23a-RPL11 interactions, which may have activated p53, resulting in spermatogonia apoptosis. These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility. The graphical abstract was available in the web of www.besjournal.com.


Subject(s)
Animals , Apoptosis/genetics , Gene Expression Regulation , Male , Mice , Ribosomal Proteins/metabolism , Signal Transduction , Spermatogonia/radiation effects
9.
Chinese Journal of Biotechnology ; (12): 2595-2602, 2021.
Article in Chinese | WPRIM | ID: wpr-887825

ABSTRACT

Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.


Subject(s)
Gene Expression Regulation , Humans , Neoplasms/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Repressor Proteins/genetics , Transcription Factors/genetics
10.
Article in English | WPRIM | ID: wpr-880327

ABSTRACT

BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.


Subject(s)
Animals , Cytoskeletal Proteins/metabolism , Female , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Male , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats , Rats, Wistar , Social Environment , Stress, Psychological/genetics
11.
Article in English | WPRIM | ID: wpr-879956

ABSTRACT

Epigenetics concerns gene regulatory mechanisms beyond DNA sequence,such as DNA methylation,histone modification,chromatin remodeling,and non-coding RNA. Epigenetic mechanisms play a key role in development,cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information,and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis,increased glucose uptake,abnormally active glutamine metabolism,and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer,and help tumor cells adapt to hypoxia microenvironment for their survival,proliferation,invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand,metabolites in tumor cells may act as cofactors,modification donors or antagonists of epigenetic enzymes,thus modulating the epigenetic landscape. On the other hand,epigenetic modifications can directly regulate the expression of metabolic enzymes,transporters,signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism,to explore their potential future applications in the treatment of tumors.


Subject(s)
Carcinogenesis , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation , Humans , Neoplasms/genetics , Tumor Microenvironment
12.
Chinese Journal of Hepatology ; (12): 1132-1136, 2021.
Article in Chinese | WPRIM | ID: wpr-922702

ABSTRACT

Hepatic fibrogenesis (HF) is the common consequence of various chronic liver diseases (CLD) induced by a variety of pathogenic factors. The mechanism of HF involves the interactions within different types of liver cells, cytokines, chemokines, cell mediators and multiple signaling pathways in a way of networks. As a result, excessive production and deposition of extracellular matrix (ECM) mainly composed of type I and type III fibril forming collagen destroys the original morphology, structure and function of the liver. The activation of hepatic stellate cells (HSCs), the major scar forming cells in liver, plays a crucial role in hepatic fibrogenesis. MicroRNAs are a group of short, single stranded, non-coding RNAs that can inhibit mRNA expression at the transcriptional and post transcriptional levels. They can be loaded and transferred as cargos by exosomes, to regulate the function of nearby and distant receptive cells. The expressions of many microRNAs such as miR-21, miR-29, miR-708, miR-101, miR-455, miR-146, miR-193 change significantly in activated HSCs, which regulate the activation, fibrogenic function, proliferation, apoptosis and autophagy of HSCs via affecting target genes expression and signaling pathway molecules. They are important substances and regulatory mechanism that mediate the initiation and progression of HF.


Subject(s)
Cell Proliferation , Gene Expression Regulation , Hepatic Stellate Cells , Humans , Liver Cirrhosis/pathology , MicroRNAs/genetics
13.
Chinese Journal of Biotechnology ; (12): 911-922, 2021.
Article in Chinese | WPRIM | ID: wpr-878603

ABSTRACT

Transcription factor-based biosensors (TFBs) play an essential role in metabolic engineering and synthetic biology. TFBs sense the metabolite concentration signals and convert them into specific signal output. They hold high sensitivity, strong specificity, brief analysis speed, and are widely used in response to target metabolites. Here we reviewe the principles of TFBs, the application examples, and challenges faced in recent years in microbial cells, including detecting target metabolite concentrations, high-throughput screening, adaptive laboratory evolutionary selection, and dynamic control. Simultaneously, to overcome the challenges in the application, we also focus on reviewing the performance tuning strategies of TFBs, mainly including traditional and computer-aided tuning strategies. We also discuss the opportunities and challenges that TFBs may face in practical applications, and propose the future research trend.


Subject(s)
Biosensing Techniques , Gene Expression Regulation , Metabolic Engineering , Synthetic Biology , Transcription Factors/metabolism
14.
Mem. Inst. Oswaldo Cruz ; 116: e200326, 2021. tab, graf
Article in English | LILACS | ID: biblio-1250363

ABSTRACT

BACKGROUND Schistosomiasis is a disease caused by Schistosoma. Due to its complex life cycle, evolutionary position and sexual dimorphism, schistosomes have several mechanisms of gene regulation. MicroRNAs (miRNAs) are short endogenous RNAs that regulate gene expression at the post-transcriptional level by targeting mRNA transcripts. OBJECTIVES Here, we tested 12 miRNAs and identified their putative targets using a computational approach. METHODS We performed the expression profiles of a set of miRNAs and their putative targets during the parasite's life cycle by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). FINDINGS Our results showed differential expression patterns of the mature miRNAs sma-miR-250; sma-miR-92a; sma-miR-new_4-3p; sma-miR-new_4-5p; sma-miR-new_5-5p; sma-miR-new_12-5p; sma-miR-new_13-3p and sma-miR-new_13-5p. Interestingly, many of the putative target genes are linked to oxidative phosphorylation and are up-regulated in adult-worms, which led us to suggest that miRNAs might play important roles in the post-transcriptional regulation of genes related to energetic metabolism inversion during parasite development. It is noteworthy that the expression of sma-miR-new_13-3p exhibited a negative correlation on SmNADH:ubiquinone oxidoreductase complex I. MAIN CONCLUSIONS Our analysis revealed putative miRNA genes related to important biological processes, such as transforming growth factor beta (TGF-β) signaling, proteasome regulation, glucose and lipid metabolism, immune system evasion and transcriptional regulation.


Subject(s)
Animals , MicroRNAs/genetics , Schistosoma mansoni/genetics , Signal Transduction , Gene Expression Regulation/genetics , Gene Expression Profiling , Life Cycle Stages/genetics
15.
Gac. méd. Méx ; 156(4): 348-351, Jul.-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1249923

ABSTRACT

Abstract Introduction: Reports of dermatological manifestations in patients with COVID-19 suggest a possible cutaneous tropism of SARS-CoV-2; however, the capacity of this virus to infect the skin is unknown. Objective: To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. Method: A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. Results: The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2. Conclusions: Our results suggest that cutaneous manifestations in patients with COVID-19 cannot be directly attributed to the virus. It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.


Resumen Introducción: Reportes de manifestaciones dermatológicas en pacientes con COVID-19 sugieren un posible tropismo cutáneo del virus SARS-CoV-2; sin embargo, se desconoce la capacidad de este virus para infectar la piel. Objetivo: Determinar la susceptibilidad de la piel a la infección por SARS-CoV-2 con base en la expresión de los factores de entrada viral ACE2 y TMPRSS2 en dicho órgano. Método: Se buscaron los genes ACE2 y TMPRSS2 en la piel, para lo cual se realizó un análisis extenso de las bases de datos de expresión genética en tejidos humanos. Asimismo, se evaluó la expresión de dichos genes en líneas celulares humanas derivadas de la piel. Resultados: Los análisis mostraron alta expresión conjunta de ACE2 y TMPRSS2 en el tracto gastrointestinal y en los riñones, pero no en la piel. Solo la línea celular de queratinocitos humanos inmortalizados HaCaT expresó niveles detectables de ACE2 y ninguna línea celular de origen cutáneo expresó TMPRSS2. Conclusiones: Los resultados sugieren que las manifestaciones dermatológicas en pacientes con COVID-19 no pueden ser atribuidas directamente al virus; es posible que sean originadas por el daño endotelial a los vasos sanguíneos cutáneos y el efecto de los mediadores inflamatorios circulantes producidos en respuesta al virus.


Subject(s)
Humans , Pneumonia, Viral/complications , Serine Endopeptidases/genetics , Skin Diseases, Viral/virology , Coronavirus Infections/complications , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Skin/virology , Cell Line , Gene Expression Regulation , Coronavirus Infections/genetics , Genetic Predisposition to Disease , Virus Internalization , Viral Tropism/physiology , Pandemics , Betacoronavirus/isolation & purification , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19
16.
Gac. méd. Méx ; 156(4): 324-329, Jul.-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1249919

ABSTRACT

Abstract In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.


Resumen En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.


Subject(s)
Humans , Pneumonia, Viral/virology , Testis/virology , Coronavirus Infections/virology , Betacoronavirus/isolation & purification , Pneumonia, Viral/physiopathology , Serine Endopeptidases/genetics , Gene Expression Regulation , Virus Latency , Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/genetics , Basigin/genetics , Pandemics , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19
17.
Biol. Res ; 53: 01, 2020. graf
Article in English | LILACS | ID: biblio-1089072

ABSTRACT

BACKGROUND: Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson's disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. RESULTS: Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. CONCLUSION: SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.


Subject(s)
Animals , Male , Mice , Parkinson Disease/metabolism , 1-Methyl-4-phenylpyridinium/toxicity , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , RNA, Long Noncoding/metabolism , Parkinson Disease/genetics , Transfection , Signal Transduction , Cells, Cultured , Gene Expression Regulation , Blotting, Western , Apoptosis , MicroRNAs , Disease Models, Animal , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding/genetics , Mice, Inbred C57BL
18.
Biol. Res ; 53: 35, 2020. graf
Article in English | LILACS | ID: biblio-1131881

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.


Subject(s)
Animals , Male , Rats , Spinal Cord Injuries/metabolism , MicroRNAs/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RNA, Circular/genetics , Inflammation/metabolism , Gene Expression Regulation , Cytokines/blood , Rats, Sprague-Dawley
19.
Braz. arch. biol. technol ; 63: e20180513, 2020. graf
Article in English | LILACS | ID: biblio-1132208

ABSTRACT

Abstract Silicon accumulation is known to improve tolerance of plants under both biotic and abiotic stress. Salinity stress is an inevitable crisis causing wide spread damage to rice leading to food insecurity. The influence of Si (1mM) on two rice cultivars cv. Ghanteswari (high accumulator) and cv.Badami (low accumulator) which differs in Si uptake potential under saline (10ds/m EC) and non- saline conditions were studied in nutrient culture. The Si transporter genes were isolated and characterized to determine their function in salinity tolerance. Under stress, there was an increase in Si accumulation, Na+/K+ ratio, electrolyte leakage, lipid peroxidation and antioxidant activities. On addition of silicon, the K+ uptake increased, membrane damage reduced and osmolytes balance improve under salinity. But, the level of resurgence was varied in both cultivars, due to their differential Si-accumulation. Molecular characterizations of Lsi1 protein revealed its involvement in the movement of ion and water and therefore prevent osmotic stress. The Lsi2 is responsible for removal of Na+, reducing salt toxicity. Silicon accumulation is responsible for maintenance of cell water status, osmotic balance and Na+ ion exclusion during high salinity. The variable relative expression of Lsi2 provides a possible explanation for differential genotypic uptake of silicon.


Subject(s)
Membrane Transport Proteins/genetics , Oryza/genetics , Silicon/metabolism , Gene Expression Regulation , Salinity , Salt Stress , Genotype
20.
Mem. Inst. Oswaldo Cruz ; 115: e190378, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1135284

ABSTRACT

BACKGROUND Key genes control the infectivity of the Schistosoma haematobium causing schistosomiasis. A method for understanding the regulation of these genes might help in developing new disease strategies to control schistosomiasis, such as the silencing mediated by microRNAs (miRNAs). The miRNAs have been studied in schistosome species and they play important roles in the post-transcriptional regulation of genes, and in parasite-host interactions. However, genome-wide identification and characterisation of novel miRNAs and their pathway genes and their gene expression have not been explored deeply in the genome and transcriptome of S. haematobium. OBJECTIVES Identify and characterise mature and precursor miRNAs and their pathway genes in the S. haematobium genome. METHODS Computational prediction and characterisation of miRNAs and genes involved in miRNA pathway from S. haematobium genome on SchistoDB. Conserved domain analysis was performed using PFAM and CDD databases. A robust algorithm was applied to identify mature miRNAs and their precursors. The characterisation of the precursor miRNAs was performed using RNAfold, RNAalifold and Perl scripts. FINDINGS We identified and characterised 14 putative proteins involved in miRNA pathway including ARGONAUTE and DICER in S. haematobium. Besides that, 149 mature miRNAs and 131 precursor miRNAs were identified in the genome including novel miRNAs. MAIN CONCLUSIONS miRNA pathway occurs in the S. haematobium, including endogenous miRNAs and miRNA pathway components, suggesting a role of this type of non-coding RNAs in gene regulation in the parasite. The results found in this work will open up a new avenue for studying miRNAs in the S. haematobium biology in helping to understand the mechanism of gene silencing in the human parasite Schistosome.


Subject(s)
Humans , Animals , Schistosoma haematobium/genetics , Schistosomiasis/parasitology , Gene Expression Regulation/genetics , Computational Biology/methods , MicroRNAs/genetics , Sequence Analysis, RNA , Transcriptome/genetics
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